N-tosyl aniline

This reaction principle has been simplified to direct Pd(II)-catalyzed N-amination/biaryl coupling routes starting (a) with 2-chloroanilines and aryl bromides in the presence of tBu3 P [204] and (b) starting with 2-bromo-(N-tosyl)anilines and iodoarenes in the presence of K2CO3 and norbomene as co-Ugand [205]. 

Starting form 2-iodo-(N-tosyl)aniline (X), the following sequence of reactions is carried out ... 

Scheme 6.37 Product range of the styrene oxide opening with anilines promoted by N-tosyl urea catalyst 37.

The same group developed an interesting intermolecular palladium-catalyzed alienation of aryliodide with N-tosyl o-iodoanilines with nucleophiles in combination with two palladium-coupling reactions [69]. In this reaction, the N-allyl(2-iodopalladium)aniline intermediate 52 underwent an intramolecular Heck reaction followed by a cross-coupling reaction with phenyl boronic acid to give the 3,3-disubstituted indoline 53 in 78% yield (Scheme 8.27). 

Two examples of such applications are outlined in Scheme 3. In the first one imidazolidinone la 10 mol% catalyzed the conjugated addition of a plethora of variously substituted N,N-disubstituted anilines to ,/fun saturated aldehydes to afford highly enantiomerically enriched /3-aryl aldehydes 5 (ee 89-97 %) in good yields (>73 %) [3]. On the other hand, the use of cationic BINAP-Cu complexes 6 (1-5 mol%) was found to be effective in the stereocontrolled 1,2-addition of indoles to the N-tosyl-a-imino ester 7 in TFIF at -78 °C [4]. 

Tetrakis(dimethylamino)titanium is a useful reagent for preparing amidines from secondary amides. From A X-thionyldiimidazole and secondary amides of boA aromatic and aliphatic carboxylic acids amidines (313 Scheme 50) are formed under mild conditions in moderate to good yields. N-Tosyl-amidines (314) can be obtained by reacting secondary thioamides (aliphatic and aromatic) with tosyl azide. Thiobenzamides have been condensed with anilines to afford amidines (315). Thioamides can be converted to amidines, e.g. (316), by treatment with ammonia in the presence of mercury acetate. ... 

N-Tosyl-substituted amines have also been used to prepare secondary diamino ethers. Petranek and Ryba (1980) reacted yV-tosylbenzylamine or the aniline analog with the dibromo derivative of dicthylene glycol to form the bis(A -tosylamino) derivatives. The tosyl blocking groups were removed by... 

Use of heterogeneous palladium catalysts, [Pd(NH3)4] /NaY and Pd]/ SBA-15, for the synthesis of 2-substituted indoles gave high conversions and selectivities (2006MI715). Changing iodoaniline to N-tosyl-2-iodoani-line produced significandy increased reaction times for fuU conversion. The heteroannulation of phenylacetylene with sulfonamide requires 6 days but only 1 day with the free aniline. 

Hegedus developed an olefin amination process that generates indoles by intramolecular nucleophilic attack of substituted amines on allylarenes (Equation 11.27). In this process, an N-tosyl arylamine attacks the coordinated olefin of an allyl group in the ortho position of the aniline, and p-hydrogen elimination generates a tautomer of indole and a reduced palladium complex. This reduced complex is then re-oxidized by quinone to regenerate the starting palladium(II), and the product tautomerizes to the final indole product. This cycle was one of the earliest catalytic olefin aminations. 

The 2,N-diallylarenes 35 are obtained (i) from 2-iodo-N-alkyl- (or acyl-) anilines 34 by Suzuki-Miyaura cross-coupling and subsequent N-allylation and (ii) from N-diallylanilines 37 by sequential Lawis-add induced aza-CiAisEN rearrangement and N-tosylation [27]. 

SCHEME 4 Heteroarmulation through heterogeneous additive-free catalysis from N-tosyl protected anilines. 

The selective N-monoalkylation of anilines with alkyl halides and alkyl tosylates under microwave irradiation has been described by Romera and coworkers (Scheme... 

N-Alkyl- and N-aryl-ketenimines are poor electrophilic partners and do not react with benzylidene-aniline or dicyclohexylcarbodiimide." The introduction of an electron-withdrawing substituent (tosyl or cyano ) on the nitrogen atom enhances the electrophilic character of the cumulene and cycloadditions to imines occur under very mild conditions (Scheme 42). In most cases, the reactions are trans stereoselective. 

A study of the effect of the structure and size of the amine radical (butylamine, dibutylamine, hexylamine, piperidine, aniline) on its reactivity in the nucleophilic replacement of tosyloxy groups in cellulose tosylate has shown (29) that this reactivity depends primarily on the basicity of the amine. TTiis assumption was confirmed by a study of the interaction of cellulose toxylates of different degrees of substitution (DS from 0.3-1.7) wit iminodiacetic and anthranilic acids 30, 31). TTie degree of substitution of the reaction products with respect to the N-carboxyalkyl(aryl)amino groups was found to be lower than that of the corresponding N-alkyl(aryl)araino derivatives. 

Finally, an alternative intramolecular Csp -N bond coupling was described by Mai [13]. In this case, the authors developed conditions for the oxidative addition of an aniline to an imine group within the same molecule 20 to arrive at 2-arylated benzimidazoles 21. The reaction is of ample scope. The mechanistic details are unclear at present and the authors propose an initial interaction between the tosyl-amido group and the hypervalent iodine reagent to initiate electrophilic amination chemistry, which is followed by an unprecedented cyclization upon the aldimine group. 

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